The US envoy to the global coalition fighting the Islamic State group has resigned in protest over President Donald Trump's abrupt decision to withdraw US troops from Syria.
Brett McGurk joins Defence Secretary Jim Mattis in an exodus of experienced national security officials.
Only 11 days ago, Mr McGurk had said it would be "reckless" to consider IS defeated and therefore would be unwise to bring American forces home.
His resignation letter was submitted on Friday to Secretary of State Mike Pompeo.
Mr McGurk, appointed to the post by President Barack Obama in 2015 and retained by President Trump, said in his resignation letter that the militants were on the run, but not yet defeated, and that the premature pullout of American forces from Syria would create the conditions that gave rise to IS.
Mr McGurk also cited gains in accelerating the campaign against IS, but that the work was not yet done.
Mr McGurk, whose resignation is effective from December 31, was planning to leave the job in mid-February after a US-hosted meeting of foreign ministers from the coalition countries, but he felt he could continue no longer after Trump's decision to withdraw from Syria and Mr Mattis' resignation.
President Trump is acting to pull all 2,000 US troops from Syria and has now declared victory over IS, contradicting his own experts' assessments. Many have called his action rash and dangerous.
Mr Mattis, perhaps the most respected foreign policy official in the administration, announced on on Thursday that he will leave by the end of February.
He told President Trump in a letter that he was departing because "you have a right to have a Secretary of Defence whose views are better aligned with yours".
The US began airstrikes in Syria in 2014, and ground troops moved in the following year to battle IS and train Syrian rebels in a country torn apart by civil war.
President Trump, in a tweet this past week, abruptly declared their mission accomplished.
The decision will fulfil President Trump's goal of bringing troops home from Syria, but military leaders have pushed back for months, arguing that the IS group remains a threat and could regroup in Syria's long-running civil war.
US policy has been to keep troops in place until the extremists are eradicated.
Mr McGurk, 45, previously served as a deputy assistant secretary of state for Iraq and Iran, and during the negotiations for the landmark Iran nuclear deal by the Obama administration, led secret side talks with Tehran on the release of Americans imprisoned there.
Mr McGurk, was briefly considered for the post of ambassador to Iraq after having served as a senior official covering Iraq and Afghanistan during President George W Bush's administration.
A former Supreme Court law clerk to the late Chief Justice William Rehnquist, Mr McGurk worked as a lawyer for the Coalition Provisional Authority in Iraq after the 2003 US-led invasion and joined President Bush's National Security Council staff, where in 2007 and 2008, he was the lead US negotiator on security agreements with Iraq.
Taking over for now for Mr McGurk will be his deputy, retired Lt Gen Terry Wolff, who served three tours of active duty in Iraq.